| Co-Investigator(Kenkyū-buntansha) |
SOTOYAMA Hiroshi Fujita Health University School of Medicine, Lecturer, 医学部, 講師 (90247643)
MATSUMURA Kaname Mie University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (70126994)
SAKAKURA Teruyo Mie University, Faculty of Medicine Professor, 名誉教授 (80073120)
YOSHIDA Kyoko (IMANAKA,KYOKO) Mie University, Faculty of Medicine, Lecturer, 医学部, 講師 (00242967)
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| Research Abstract |
Tenascin-C and cellular fibronectin are known as onco-fetal extracellular matrix (ECM) proteins expressed in embryonic tissues and cancer stroma. These molecules are produced by mesenchymal and epithelial cells under such microenvironments, and deposits in the tissues in higher levels than in normal adult tissues. Furthermore, there are various splicing variants of these molecules, which seem to be exclusively expressed in cacer tissues. In this study, we explore specificities of cancer stroma, produce a monoclonal antibody specific to cancer stroma, and develop the applicable methods for cancer treatments. 1) First we studied specific expression of known ECM proteins in cancer stroma. 2) we attempted to produce monoclonal antibodies specific to cancer stroma by immunization of extracted proteins from the stroma. 3) we also tested whether, after injection of fluorescence-lableled antibody in tumor-bearing mice, the antibody was accumulated in cancer stroma. For 1, we found that deposition of TN-C and cellular FN produced by cancer cells themselves are relatively specific in cancer stroma, which may play important roles in cancer progression. 2) we produced new monoclonal antibodies against cancer stromal proteins, possibly FN and proteoglycan. 3) we produced high affinity-monoclonal antibodies against TN-C by immunization to TNC-null mice. After the injection, the antibody was exclusively accumulated in stroma of mouse mammary tumor. Furthermore, antibodies against a spliced site of TNC which is included in cancer stromal one but not in normal tissue, were produced. The antibody showed positive reaction to cancer stroma, but negative in normal tissues.
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